Effects of Ba2+ on SK&F 96365-sensitive Sustained Contraction of Rat Pulmonary Artery

Abstract

Abstract The effects of Ba2+ on receptor-mediated sustained contraction of rat pulmonary artery and guinea-pig oesophageal muscularis mucosae were studied in-vitro. In rat isolated pulmonary artery, sustained contraction induced by noradrenaline (1 μm) was resistant to nicardipine (1 μm), but this same sustained contraction was completely inhibited by SK&F 96365 (30 μm), a blocker of voltage-dependent L-type Ca2+ channels and receptor-activated Ca2+ influx. The SK&F 96365-sensitive sustained contraction induced by noradrenaline (1 μM) may be due primarily to Ca2+ influx through receptor-activated Ca2+ channels resistant to nicardipine. Cumulatively applied BaCl2 (0.1 — 10 mM) increased the noradrenaline (1 μM)-induced sustained contraction of the pulmonary arterial preparation in the absence of nicardipine, but in the presence of nicardipine (1 μM), BaCl2 (0.1 — 3 mM) did not affect this contraction. A higher concentration of BaCl2 (10 mM), however, weakly inhibited the noradrenaline (1 μM)-induced tone. In addition, BaCl2 (3–10 mM) increased the tone induced by KCl (60 mM), and the BaCl2-elevated KCl tone was markedly inhibited by nicardipine (1 μM) treatment. In the guinea-pig isolated oesophageal muscularis mucosae, sustained contraction induced by acetylcholine (3 μM) was resistant to nicardipine (1 μM) but was returned to its basal level by SK&F 96365 (30–60 μM). The SK&F 96365-sensitive, acetylcholine-induced sustained contraction of the oesophageal muscularis mucosae is also likely to link with receptor-activated Ca2+ channels resistant to nicardipine. In contrast to the rat pulmonary artery, cumulatively applied BaCl2 (0.3–10 mM) inhibited the acetylcholine (3 μM)-induced sustained contraction of the oesophageal muscularis mucosae in a concentration-dependent manner in the presence of nicardipine (1 μM). In conclusion, Ba2+ presumably activates voltage-dependent Ca2+ channels by depolarizing plasma membrane and also passes through voltage-dependent Ca2+ channels to contract the pulmonary artery in the absence of nicardipine, and Ba2+ also has a minor effect on the nicardipine-resistant, SK&F 96365-sensitive sustained contraction induced by noradrenaline in rat isolated pulmonary artery.